Objective: To determine the rates of synthesis and degradation of collagen and of acid mucopolysaccharides in the course of the development of dietary cirrhosis in the rat, and to ascertain how this process is modified by chronic ethanol consumption. Methods: Dietary cirrhosis will be induced in rats and the rates of synthesis and degradation of collagen in the course of the development of cirrhosis determined by the double labelling method of Dehlinger and Schimke. The findings will be correlated with histological, histochemical and autoradiographic determinations. In parallel experiments, rats will be treated identically but will receive ethanol in increasing concentrations in the drinking water. On the basis of these experiments mucopolysaccharide components, tentatively identified on a histochemical basis as being associated with the deposited collagen, will be studied in a similar manner. The source of the label will be radioactive sulfate or carbon on the one hand and tritium on the other. Depending on the mucopolysaccharide element to be studied, the material will be identified after protein digestion, column chromatography and electrophoretic separation, and treated with the specific enzyme for identification of the appropriate radioactive moiety. It is anticipated that this will provide a description of the biochemical sequence which describes the connective tissue changes seen in cirrhosis, and determine how this process may be modified by ethanol.